ABSTRACT
Biomechanical stress may exacerbate inflammation in psoriatic arthritis (PsA). This study aimed to investigate disease activity, work disability, and drug response/retention rates in PsA patients among two different occupation's types: blue-collar workers (BCol) with manual labor versus white-collar workers (WCol) with sedentary occupations. PsA patients registered in the Swiss cohort (SCQM) were classified as BCol or WCol workers and assessed at the initiation of a biologic or targeted synthetic disease-modifying anti-rheumatic drug (b-/tsDMARD). We compared the baseline characteristics at treatment start and the DAS28-CRP for the 1-year remission. Treatment retention was investigated using Kaplan-Meier curves and Cox regression analysis. Multivariable models were adjusted for potential confounders. Of 564 patients, 29% were BCol, and 71% were WCol workers. Baseline disease activity was comparable between both groups. BCol workers were predominantly male (79.8%) and more work disabled at baseline (84.0% vs. 27.9%; p < 0.01). One hundred seventy-four treatment courses (TCs) of 165 PsA patients were included for longitudinal analysis. Occupation did not significantly influence the achievement of DAS28-CRP remission at 1 year. Kaplan-Meier analysis (n = 671) indicated longer retention for BCol workers (mean retention duration: 3.15 years vs. 2.15 years, (p = 0.006). However, adjusted Cox regression analysis did not corroborate these findings. This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients, while treatment response seems to be unaffected by the patients' occupation type. Additional research is required to thoroughly comprehend the relationship between physical workload, disease activity, and treatment outcomes. Key Points ⢠This study indicates that physically demanding occupations correlate with increased rates of work disability among PsA patients. ⢠The treatment response among of PsA patients seems unaffected by the patients' occupation type.
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In this study, we optimized the dissociation of synovial tissue biopsies for single-cell omics studies and created a single-cell atlas of human synovium in inflammatory arthritis. The optimized protocol allowed consistent isolation of highly viable cells from tiny fresh synovial biopsies, minimizing the synovial biopsy drop-out rate. The synovium scRNA-seq atlas contained over 100,000 unsorted synovial cells from 25 synovial tissues affected by inflammatory arthritis, including 16 structural, 11 lymphoid, and 15 myeloid cell clusters. This synovial cell map expanded the diversity of synovial cell types/states, detected synovial neutrophils, and broadened synovial endothelial cell classification. We revealed tissue-resident macrophage subsets with proposed matrix-sensing (FOLR2+COLEC12high) and iron-recycling (LYVE1+SLC40A1+) activities and identified fibroblast subsets with proposed functions in cartilage breakdown (SOD2highSAA1+SAA2+SDC4+) and extracellular matrix remodeling (SERPINE1+COL5A3+LOXL2+). Our study offers an efficient synovium dissociation method and a reference scRNA-seq resource, that advances the current understanding of synovial cell heterogeneity in inflammatory arthritis.
ABSTRACT
Analysing complex diseases such as chronic inflammatory joint diseases (CIJDs), where many factors influence the disease evolution over time, is a challenging task. CIJDs are rheumatic diseases that cause the immune system to attack healthy organs, mainly the joints. Different environmental, genetic and demographic factors affect disease development and progression. The Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) Foundation maintains a national database of CIJDs documenting the disease management over time for 19'267 patients. We propose the Disease Activity Score Network (DAS-Net), an explainable multi-task learning model trained on patients' data with different arthritis subtypes, transforming longitudinal patient journeys into comparable representations and predicting multiple disease activity scores. First, we built a modular model composed of feed-forward neural networks, long short-term memory networks and attention layers to process the heterogeneous patient histories and predict future disease activity. Second, we investigated the utility of the model's computed patient representations (latent embeddings) to identify patients with similar disease progression. Third, we enhanced the explainability of our model by analysing the impact of different patient characteristics on disease progression and contrasted our model outcomes with medical expert knowledge. To this end, we explored multiple feature attribution methods including SHAP, attention attribution and feature weighting using case-based similarity. Our model outperforms temporal and non-temporal neural network, tree-based, and naive static baselines in predicting future disease activity scores. To identify similar patients, a k-nearest neighbours regression algorithm applied to the model's computed latent representations outperforms baseline strategies that use raw input features representation.
ABSTRACT
BACKGROUND: The Spondyloarthritis Research Consortium of Canada (SPARCC) developers have created web-based calibration modules for the SPARCC MRI sacroiliac joint (SIJ) scoring methods. We aimed to test the impact of applying these e-modules on the feasibility and reliability of these methods. METHODS: The SPARCC-SIJ RETIC e-modules contain cases with baseline and follow-up scans and an online scoring interface. Visual real-time feedback regarding concordance/discordance of scoring with expert readers is provided by a colour-coding scheme. Reliability is assessed in real time by intraclass correlation coefficient (ICC), cases being scored until ICC targets are attained. Participating readers (n=17) from the EuroSpA Imaging project were randomised to one of two reader calibration strategies that each comprised three stages. Baseline and follow-up scans from 25 cases were scored after each stage was completed. Reliability was compared with a SPARCC developer, and the System Usability Scale (SUS) assessed feasibility. RESULTS: The reliability of readers for scoring bone marrow oedema was high after the first stage of calibration, and only minor improvement was noted following the use of the inflammation module. Greater enhancement of reader reliability was evident after the use of the structural module and was most consistently evident for the scoring of erosion (ICC status/change: stage 1 (0.42/0.20) to stage 3 (0.50/0.38)) and backfill (ICC status/change: stage 1 (0.51/0.19) to stage 3 (0.69/0.41)). The feasibility of both e-modules was evident by high SUS scores. CONCLUSION: The SPARCC-SIJ RETIC e-modules are feasible, effective knowledge transfer tools, and their use is recommended before using the SPARCC methods for clinical research and tria.
Subject(s)
Sacroiliac Joint , Spondylarthritis , Humans , Canada , Magnetic Resonance Imaging/methods , Reproducibility of Results , Sacroiliac Joint/diagnostic imaging , Sacroiliac Joint/pathology , Spondylarthritis/diagnosis , Spondylarthritis/pathologySubject(s)
Ultrasonography , Humans , Ultrasonography/methods , Range of Motion, Articular/physiology , Female , MaleABSTRACT
BACKGROUND: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. OBJECTIVES: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). METHODS: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. RESULTS: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87-9.68) compared to CSTs (7.08, CI 5.39-9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. CONCLUSION: Females were associated with a significantly higher rate of ADRs and drug-related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient-tailored management of psoriasis.
Subject(s)
Biological Products , Psoriasis , Adult , Humans , Male , Female , Middle Aged , Switzerland/epidemiology , Sex Characteristics , Psoriasis/drug therapy , Psoriasis/chemically induced , Biological Factors , Biological Products/adverse effects , Registries , Treatment OutcomeABSTRACT
OBJECTIVE: To characterise the population fulfilling the Assessment of SpondyloArthritis international Society (ASAS) consensus definition of early axial spondyloarthritis (axSpA) and to determine the effectiveness of a first tumour necrosis factor inhibitor (TNFi) in early versus established axSpA in a large observational registry. METHODS: A total of 3064 patients with axSpA in the Swiss Clinical Quality Management registry with data on duration of axial symptoms were included (≤2 years=early axSpA, N=658; >2 years=established axSpA, N=2406). Drug retention was analysed in patients starting a first TNFi in early axSpA (N=250) versus established axSpA (N=874) with multiple-adjusted Cox proportional hazards models. Adjusted logistic regression analyses were used to determine the achievement of the ASAS criteria for 40% improvement (ASAS40) at 1 year. RESULTS: Sex distribution, disease activity, impairments of function and health-related quality of life were comparable between patients with early and established axSpA. Patients with established disease were older, had more prevalent axial radiographical damage and had a higher impairment of mobility. A comparable TNFi retention was found in early versus established disease after adjustment for age, sex, human leucocyte antigen-B27 status, education, body mass index, smoking, elevated C reactive protein and sacroiliac inflammation on MRI (HR 1.05, 95% CI 0.78 to 1.42). The adjusted ASAS40 response was similar in the two groups (OR 1.09, 95% CI 0.67 to 1.78). Results were confirmed in the population fulfilling the ASAS classification criteria. CONCLUSION: Considering the recent ASAS definition of early axSpA, TNFi effectiveness seems comparable in early versus established disease.
Subject(s)
Axial Spondyloarthritis , Tumor Necrosis Factor Inhibitors , Humans , Cohort Studies , Consensus , Quality of Life , Registries , Treatment Outcome , Tumor Necrosis Factor Inhibitors/therapeutic useABSTRACT
Although patients with rheumatoid arthritis (RA) typically exhibit symmetrical joint involvement, some patients develop alternative disease patterns in response to treatment, suggesting that different molecular mechanism may underlie disease progression depending on joint location. Here, we identify joint-specific changes in RA synovium and synovial fibroblasts (SF) between knee and hand joints. We show that the long non-coding RNA HOTAIR, which is only expressed in knee SF, regulates more than 50% of this site-specific gene expression in SF. HOTAIR is downregulated after stimulation with pro-inflammatory cytokines and is expressed at lower levels in knee samples from patients with RA, compared with osteoarthritis. Knockdown of HOTAIR in knee SF increases PI-Akt signalling and IL-6 production, but reduces Wnt signalling. Silencing HOTAIR inhibits the migratory function of SF, decreases SF-mediated osteoclastogenesis, and increases the recruitment of B cells by SF. We propose that HOTAIR is an important epigenetic factor in joint-specific gene expression in RA.
Subject(s)
Arthritis, Rheumatoid , Osteoarthritis , RNA, Long Noncoding , Humans , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/metabolism , Fibroblasts/metabolism , Gene Expression , Osteoarthritis/genetics , Osteoarthritis/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Synovial Fluid/metabolism , Synovial Membrane/metabolismABSTRACT
OBJECTIVE: A lack of representation in pivotal trials currently limits guidance for the use of biological disease-modifying anti-rheumatic drugs (bDMARDs) in psoriatic arthritis (PsA) patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with low vs high number of affected joints. METHODS: PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or < 3 swollen joints or high joint count patients (HJC) with > =3 joints in both categories. We studied drug retention as a joint count independent effectiveness variable in LJC and HJC patients in univariate and multivariable adjusted Cox regression models. RESULTS: 197 LJC patients differed not only in joint counts, but also had lower enthesitis scores, less often dactylitis, less disability and a better health related quality of life at first bDMARD initiation than 190 HJC patients. However, LJC were less often on conventional synthetic (cs) DMARDs. Despite these differences at baseline, bDMARD retention was not significantly different between LJC and HJC in both crude and adjusted analyses (Hazard Ratio (HR) 1.09 [0.76-1.58], p= 0.52). Furthermore, bDMARD retention was significantly better (HR 0.63 [0.47-0.85], p< 0.002) when administered with csDMARD co-therapy. CONCLUSIONS: Biological DMARDs were similarly effective in terms of drug retention in patients with low and high joint counts. In the setting of absent remission and a significant disease burden, bDMARDs should not be withheld from patients because they exhibit only a low joint count.
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OBJECTIVE: Obesity is an important comorbidity in axial spondyloarthritis (axSpA); however, the prevalence of obesity in axSpA compared with the general population and associated socioeconomic factors remain unknown. METHODS: This repeated cross-sectional study compared BMI (kg/m2) groups of patients with axSpA to the Swiss population at 3 timepoints (2007, 2012, and 2017). BMI categories were compared by different age, sex, and education categories using the chi-square goodness of fit test. Unpaired, 1-sided t tests were used to compare the BMI in patients with axSpA between the different timepoints. RESULTS: Compared to the general population, patients with axSpA had a higher proportion of overweight and obesity: 18.9% of all patients with axSpA were obese, compared to 11.3% of the Swiss population in 2017. Comparison of BMI groups within sex, age, and education groups consistently showed a trend toward higher rates of overweight and obesity in axSpA. Further, patients with axSpA, especially females, showed a trend of increasing BMI over the studied 10 years. At every time point, overweight and obese patients were significantly more likely to be male, were older, and had higher disease activity than patients with normal weight. Obesity was associated with a deprived socioeconomic status as indicated by a higher proportion of patients with manual labor jobs and lower levels of education. CONCLUSION: The prevalence of obesity was significantly higher among patients with axSpA compared to the Swiss population, with socially disadvantaged individuals being the most affected. There is an urgent need to initiate prevention strategies for obesity in patients with axSpA.
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OBJECTIVE: To investigate sex differences in spinal radiographic progression in axial spondyloarthritis (axSpA). METHODS: AxSpA patients in the Swiss Clinical Quality Management cohort with available spinal radiographs every 2 years were included. Paired radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Progression was defined as an increase of ≥2 mSASSS units in 2 years. The relationship between sex and progression was investigated with binomial generalised estimating equation models, considering baseline spinal damage as an intermediate covariate. Additional analyses included adjustments for explanatory variables and multiple imputations for missingness. RESULTS: In a total of 505 axSpA patients (317 men and 188 women), mean±SD radiographic progression over 2 years was 1.0±2.8 years in men and 0.3±1.1 years in women (p<0.001). Male sex was associated with enhanced progression in a small model not including baseline damage (OR 3.41, 95% CI 1.87 to 6.21). Both a direct effect of male sex on spinal progression, and an indirect effect, via enhancement of baseline spinal damage were significant (OR 2.06, 95% CI 1.15 to 3.67 and OR 1.04, 95% CI 1.01 to 1.07, respectively). A significant impact of male sex on spinal radiographic progression was still demonstrated after multiple adjustments for covariates known to potentially affect spinal radiographic progression (OR 1.97, 95% CI 1.04 to 3.71). CONCLUSIONS: Spinal radiographic progression in axSpA is more severe in men than in women, with three times higher odds of progression in male patients and an effect that is mediated in part through an increase in baseline radiographic damage.
Subject(s)
Spondylitis, Ankylosing , Humans , Male , Female , Switzerland/epidemiology , Disease Progression , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/epidemiology , Spine/diagnostic imaging , Cohort StudiesABSTRACT
OBJECTIVE: As anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA). METHODS: AxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values. RESULTS: A total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years. CONCLUSION: Although anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression. Key Points ⢠Anaemia is associated with higher disease activity and more severely impaired physical function, mobility and quality of life in axSpA. ⢠Anaemia does not provide an additional value to ASDAS for prediction of spinal radiographic progression.
Subject(s)
Anemia , Spondylarthritis , Spondylitis, Ankylosing , Humans , Male , Anemia/complications , Anemia/diagnostic imaging , Disease Progression , Prospective Studies , Quality of Life , Registries , Severity of Illness Index , Switzerland , FemaleABSTRACT
BACKGROUND: Within the spectrum of spondyloarthritides, axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) present with overlapping features. Axial involvement in PsA (axial PsA) is treated according to recommendations for axSpA, as specific studies in axial PsA are scarce. We compared characteristics of patients with axSpA (particularly of patients with axSpA and concomitant psoriasis (pso)) with those of patients with axial PsA. METHODS: Patients with axSpA and PsA in the Swiss Clinical Quality Management (SCQM) registry were included if information on pso and axial involvement was available. Patients with AxSpA were stratified by axSpA with and without pso (axSpA±pso) and patients with PsA were stratified to axial PsA or strictly peripheral PsA. RESULTS: Previous or current psoriasis was observed in 479/4489 patients with axSpA (10.7%). Of 2631 patients with PsA, 1153 (43.8%) presented with axial involvement (opinion of the treating rheumatologist). Compared with patients with axSpA+pso, patients with axial PsA were older at symptom onset and at inclusion in SCQM, were less frequently HLA-B27 positive, had back pain less frequently and a higher prevalence of dactylitis and peripheral arthritis. A positive family history of pso or PsA was more frequent in axial PsA, while a positive family history of axSpA was more frequent in patients with axSpA+pso. Disease activity, function and mobility were comparable in axSpA+pso versus axial PsA. CONCLUSION: Patients with axial PsA differ from patients with axSpA+pso in important demographic and clinical characteristics, and genetically, but present with a comparable disease burden. Treatment studies specifically dedicated to axial PsA seem warranted.
Subject(s)
Arthritis, Psoriatic , Axial Spondyloarthritis , Psoriasis , Spondylarthritis , Humans , Arthritis, Psoriatic/complications , Arthritis, Psoriatic/epidemiology , Arthritis, Psoriatic/therapy , Spondylarthritis/complications , Spondylarthritis/diagnosis , Spondylarthritis/epidemiology , Psoriasis/complications , Psoriasis/epidemiology , RegistriesABSTRACT
OBJECTIVES: To analyse whether time-varying treatment with tumour necrosis factor inhibitors (TNFi) in radiographic axial spondyloarthritis (r-axSpA) has a differential impact on structural damage progression on different spinal segments (cervical versus lumbar spine). METHODS: Patients with r-axSpA in the Swiss Clinical Quality Management cohort were included if cervical and lumbar radiographs were available at intervals of 2 years for a maximum of 10 years. Paired radiographs were scored by two calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The relationship between TNFi use and progression in the cervical and the lumbar spine was analysed using generalised estimating equation models and adjustment for potential confounding. Radiographic progression per spinal segment was defined as an increase of ≥ 1 mSASSS unit or by the formation of ≥ 1 new syndesmophyte over 2 years. RESULTS: Mean ± SD symptom duration was 13.8 ± 9.8 years. Mean ± SD mSASSS progression per radiographic interval was 0.41 ± 1.69 units in the cervical spine and 0.45 ± 1.45 units in the lumbar spine (p = 0.66). Prior use of TNFi significantly reduced the odds of progression in the cervical spine by 68% (OR 0.32, 95% CI 0.14-0.72), but not in the lumbar spine (OR 0.99, 95% CI 0.52-1.88). A more restricted inhibition of progression in the lumbar spine was confirmed after multiple imputation of missing covariate data (OR 0.43, 95% CI 0.24-0.77 and 0.85, 95% CI 0.51-1.41, for the cervical and lumbar spine, respectively). It was also confirmed with progression defined as formation of ≥ 1 syndesmophyte (OR 0.31, 95% CI 0.12-0.80 versus OR 0.56, 95% CI 0.26-1.24 for the cervical and lumbar spine, respectively). CONCLUSION: Disease modification by treatment with TNFi seems to more profoundly affect the cervical spine in this r-axSpA population with longstanding disease. Site-specific analysis of spinal progression might, therefore, improve detection of disease modification in clinical trials in axSpA.
Subject(s)
Spondylarthritis , Spondylitis, Ankylosing , Humans , Disease Progression , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Severity of Illness Index , Spondylarthritis/diagnostic imaging , Spondylarthritis/drug therapy , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/drug therapy , Spondylitis, Ankylosing/pathology , Switzerland , Tumor Necrosis Factor Inhibitors/therapeutic use , Longitudinal StudiesABSTRACT
OBJECTIVE: To explore the impact of the human leucocyte antigen (HLA)-B27 on the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). METHODS: A total of 1109 patients with available HLA-B27 status (831 B27+ patients and 278 B27- patients) fulfilling the Assessment of Spondyloarthritis international Society classification criteria for axSpA from the prospective Swiss Clinical Quality Management Registry initiating a first TNFi were included. Drug retention was investigated with multiple adjusted Cox proportional hazard models with imputation of missing values. Multiple-adjusted logistic regression analyses were used to assess the proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year. RESULTS: B27+ and B27- patients differed with regard to age, sex, BASDAI, C-reactive protein (CRP), body mass index, enthesitis, uveitis, and classification status. After adjustment for potential confounders for the relationship between HLA-B27 and drug effectiveness (sex and family history of spondyloarthritis), a higher risk of drug discontinuation was found in B27- patients (HR 1.53, 95% CI 1.27-1.83). This difference decreased after additional adjustment for parameters which may act as mediators (HR 1.30, 95% CI 1.30-1.55). Male sex and elevated C-reactive protein (CRP) levels were consistently associated with longer retention. Comparable results were obtained for BASDAI50 responses. CONCLUSION: The HLA-B27 genotype is an important predictor of treatment effectiveness. Male sex and CRP seem, however, to better describe variability of response in individual patients. This data may help avoiding potential discrimination of B27- individuals with regard to TNFi initiation. Key Points ⢠HLA-B27 is a predictor of effectiveness of TNF inhibitors in axial spondyloarthritis. ⢠Variability of response in individual patients is better defined by sex and objective markers of disease activity, such as C-reactive protein.
Subject(s)
Axial Spondyloarthritis , Spondylarthritis , Spondylitis, Ankylosing , Humans , Male , Tumor Necrosis Factor Inhibitors/therapeutic use , Spondylitis, Ankylosing/drug therapy , Spondylitis, Ankylosing/genetics , HLA-B27 Antigen/genetics , C-Reactive Protein , Switzerland , Prospective Studies , Spondylarthritis/drug therapy , Spondylarthritis/genetics , RegistriesABSTRACT
CME Rheumatology 26: Bone Marrow Edema of the Sacro-Iliac Joint = Spondyloarthritis? What the General Practicioner Should Know Abstract. Axial spondyloarthritis is a chronic inflammatory joint disease mainly involving the sacroiliac joints (ISG) and the spine. The diagnosis can be made early due to acute inflammatory changes in the ISG on magnetic resonance imaging (MRI). Radiographs of the ISG do not help in early diagnosis because structural damage is not apparent on radiographs until an advanced stage. In recent years, however, several studies have shown that bone marrow edema - hyperintense signals (= bright spots) as a possible MRI correlate for inflammation - does not specifically occur in axial spondyloarthritis, but can also be seen in healthy people, athletes, people with high mechanical stress (e.g. military recruits) and postpartum women. The diagnosis of axial spondyloarthritis should therefore never be based solely on an MRI finding, but must always include the overall clinical context.
Subject(s)
Rheumatology , Spondylarthritis , Female , Humans , Sacroiliac Joint/diagnostic imaging , Bone Marrow , Spondylarthritis/diagnosis , Edema/etiologyABSTRACT
OBJECTIVE: To compare the likelihood of achieving remission between men and women with rheumatoid arthritis (RA) after starting their first biologic or targeted synthetic disease-modifying anti-rheumatic drug (b/tsDMARD). METHODS: This cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry included RA patients starting their first b/tsDMARD (1997-31/04/2018). The odds of achieving remission at ≤12-months, defined by disease activity score 28-joints (DAS28) <2.6, were compared between men and women. Secondary analyses were adjusted for age and seropositivity, and we investigated potential mediators or factors that could explain the main findings. RESULTS: The study included 2839 (76.3%) women and 883 (23.7%) men with RA. Compared to women, men were older at diagnosis and b/tsDMARD start, but had shorter time from diagnosis to b/tsDMARD (3.4 versus 5.0 years, p<0.001), and they had lower DAS28 at b/tsDMARD start. Compared to women, men had 21% increased odds of achieving DAS28-remission, with odds ratio (OR) 1.21, 95% confidence interval (CI) 1.02-1.42. Adjusting for age and seropositivity yielded similar findings (adjusted OR 1.24, 95%CI 1.05-1.46). Analyses of potential mediators suggested that the observed effect may be explained by the shorter disease duration and lower DAS28 at treatment initiation in men versus women. CONCLUSION: Men started b/tsDMARD earlier than women, particularly regarding disease duration and disease activity (DAS28), and had higher odds of reaching remission. This highlights the importance of early initiation of second line treatments, and suggests to target an earlier stage of disease in women to match the benefits observed in men.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biological Products , Humans , Male , Female , Cohort Studies , Switzerland/epidemiology , Arthritis, Rheumatoid/diagnosis , Antirheumatic Agents/therapeutic use , Biological Products/therapeutic use , Remission Induction , Treatment Outcome , Severity of Illness IndexABSTRACT
OBJECTIVES: To analyse the effect of tumour necrosis factor inhibitors (TNFi) on sacroiliac joint (SIJ) radiographic progression in axial spondyloarthritis (axSpA). METHODS: Patients with axSpA in the Swiss Clinical Quality Management cohort with up to 12 years of follow-up and radiographic assessments every 2 years were included. SIJs were scored by two readers according to the modified New York criteria blinded to chronology. The relationship between TNFi use before or during a 2-year radiographic interval and SIJ progression was investigated using generalised estimating equation models with adjustment for potential confounding. Progression was defined as worsening of ≥1 grade in ≥1 SIJ and ignoring a change from 0 to 1 over 2 years, if both readers agreed. A third reading of radiographs was integrated in sensitivity analyses. RESULTS: A total of 515 patients with axSpA contributed to data for 894 radiographic intervals (24 progression events). In patients with complete covariate data, prior use of TNFi reduced the odds of progression (OR 0.21, 95% CI 0.07 to 0.65). A comparable effect was found for use of TNFi for ≥1 year within a 2-year radiographic interval (OR 0.21, 95% CI 0.08 to 0.55). The inhibitory impact of TNFi was confirmed if progression was demonstrated in 2/3 readings: OR 0.50, 95% CI 0.28 to 0.89 and OR 0.46, 95% CI 0.27 to 0.78 for TNFi treatment before and for ≥1 year within the interval, respectively. CONCLUSION: TNFi are associated with deceleration of SIJ radiographic progression in patients with axSpA if treatment is continued for ≥1 year.
Subject(s)
Axial Spondyloarthritis , Spondylarthritis , Humans , Sacroiliac Joint/diagnostic imaging , Sacroiliac Joint/pathology , Tumor Necrosis Factor Inhibitors/therapeutic use , Spondylarthritis/diagnosis , Spondylarthritis/drug therapy , Spondylarthritis/pathology , Severity of Illness Index , RegistriesABSTRACT
OBJECTIVE: To assess the impact of elevated body mass index (BMI) in the achievement of minimal disease activity (MDA) and several definitions of remission in patients with psoriatic arthritis (PsA) in Switzerland. Secondarily, to assess the overlapping across the study outcomes. METHODS: This observational cohort study in the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry included patients with PsA starting their first biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) from 1997 to 30 June 2018. Exposure was BMI category at b/tsDMARD start: overweight, obese, and normal weight (reference). Logistic regression was used to assess the achievement of MDA and remission at ≤12 months, as well as treatment persistence at 1 year, in overweight patients and patients with obesity compared with the normal weight group. Remission was defined by Disease Activity for Psoriatic Arthritis (DAPSA), clinical DAPSA (cDAPSA) and 28-joint Disease Activity Score (DAS28). Additionally, overlapping across study outcomes was investigated. RESULTS: The study included 306 (39.5%) normal weight patients, 285 (36.8%) overweight patients and 183 (23.6%) patients with obesity. Compared with the normal weight group, patients with obesity had lower odds of achieving MDA at ≤12 months (adjusted OR (ORadj) 0.45, 95% CI 0.24 to 0.82). This was consistent with the observed reduced odds of achieving DAPSA-remission (ORadj 0.42, 95% CI 0.21 to 0.85), cDAPSA-remission (ORadj 0.51, 95% CI 0.27 to 0.96) and DAS28-remission (ORadj 0.51, 95% CI 0.32 to 0.81) in patients with obesity versus normal weight patients. Among the 125 patients achieving MDA, the majority (81.8% normal weight, 80.0% overweight, 78.9% obese) achieved cDAPSA-remission. No differences were observed in the odds to achieving treatment persistence between the BMI strata. CONCLUSIONS: Obesity halved the likelihood of achieving MDA and remission in patients with PsA with b/tsDMARDs compared with those with normal weight, while it did not impact treatment persistence. High overlapping of patients achieving the outcomes MDA and cDAPSA-remission was observed across every BMI group.